ACF在结肠癌早期病变中的变化及其与PPAR-γ和β-catenin的关系

目的: 观察结肠癌前病变序列的增殖凋亡演变过程及其与PPAR-γ、β-catenin异常表达的关系.方法: 选用SPF级SD大鼠,经改良的DMH结肠肿瘤诱导方法诱导结肠ACF和腺瘤,然后对"正常-ACF-腺瘤"序列各阶段的组织进行免疫组织化学分析其PPAR-γ和β-catenin的表达,同时选择Ki-67表示增殖水平,Bcl-2表示凋亡水平.结果: 在DMH诱导的"正常-ACF-腺瘤"序列中,Ki-67在"正常-ACF"转变阶段即出现异常高表达,呈整个隐窝广泛分布,显著高于正常隐窝,而接近腺瘤组织. Bcl-2则在"ACF-腺瘤"转变阶段才出现异常高表达,呈广泛的胞质阳性颗粒. PPAR-γ在"正常-ACF"转化阶段发生广泛的高表达,呈广泛的核阳性.β-catenin则是在"ACF-腺瘤"转化阶段出现异常表达,呈广泛的核阳性.结论: 在"正常-ACF"转化阶段主要是增殖水平的升高,而且可能与PPAR-γ的异常表达有关. 在"ACF-腺瘤"转化阶段主要是凋亡抑制增加,β-catenin与Bcl-2同期出现异常表达对腺瘤的形成可能有一定的协同作用.

Changes of aberrant crypt foci in early colon cancer and its relationship with PPAR-γ and β-catenin

AIM: To observe the progression of proliferation and apoptosis of colorectal preneoplastic sequence,and to explore the potential role of abnormal expression pattern of PPAR-γ and β-catenin in the preneoplastic sequence.METHODS: Colorectal ACFs and adenomas were induced using a modified DMH-induced carcinogenesis method in SD rats. The expression patterns of PPAR-γ and β-catenin in colorectal preneoplastic sequence were detected using immumohistochemisty. Proliferation and apoptosis of preneoplastic sequence were analyzed using Ki-67 and Bcl-2.RESULTS: In the "Normal-ACF-Adenoma" sequence induced by DMH,abnormal expression of Ki-67 occurred at the transformation stage of "Normal-ACF". Positive nucleuses of Ki-67 distributed extensively within the aberrant crypt,differing from normal crypt significantly and similar to adenoma. Abnormally high expression of Bcl-2 appeared until ACF transformed to adenoma,presenting broad positive granules in the cytoplasm. PPAR-γ,as Ki-67 did,abnormally expressed during the "Normal-ACF" shift with extensive distribution of positive nucleuses. Β-catenin,as Bcl-2 did,presented with different positive location and density until the transformation of "ACF-Adenoma" with evident positive nucleuses.CONCLUSION: In the stage of "Normal-ACF",the main abnormality is higher proliferation rate found in aberrant crypt than normal crypt,and this change might be correlated to abnormal expression of PPAR-γ. Depression of apoptosis became obvious in the stage of "ACF-Adenoma",and the elevated expression of β-catenin and Bcl-2 might have a synergic role in the formation of adenoma.